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Molecular Cancer
Published in: Molecular Cancer 1/2013

Open Access 01-12-2013 | Short communication

Phospholipid Scramblase 1, an interferon-regulated gene located at 3q23, is regulated by SnoN/SkiL in ovarian cancer cells

Authors: Karthik M. Kodigepalli, Pavana Anur, Paul Spellman, Peter J. Sims, Meera Nanjundan

Published in: Molecular Cancer | Issue 1/2013

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Abstract

Background

Treatment of advanced stage ovarian cancer continues to be challenging due to acquired drug resistance and lack of early stage biomarkers. Genes identified to be aberrantly expressed at the 3q26.2 locus (i.e. SnoN/SkiL) have been implicated in ovarian cancer pathophysiology. We have previously shown that SnoN expression is increased in advanced stage ovarian cancers and alters cellular response to arsenic trioxide (As2O3).

Findings

We now demonstrate increased DNA copy number levels (TCGA data) of phospholipid scramblase 1 (PLSCR1, located at 3q23) whose transcript expression in ovarian cell lines is highly correlated with SnoN mRNA. Interestingly, SnoN can modulate PLSCR1 mRNA levels in the absence/presence of interferon (IFN-2α). Both IFN-2α and As2O3 treatment can modulate PLSCR1 mRNA levels in ovarian carcinoma cells. However, SnoN siRNA does not lead to altered PLSCR1 protein implicating other events needed to modulate its protein levels. In addition, we report that PLSCR1 can modulate aspects of the As2O3 cellular response.

Conclusions

Our findings warrant further investigation into the role of PLSCR1 in ovarian cancer development and chemoresistance.
Appendix
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Literature
1.
Bast RC, Hennessy B, Mills GB: The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009, 9 (6): 415-428. 10.1038/nrc2644.PubMedCentralCrossRefPubMed
2.
Nanjundan M, Nakayama Y, Cheng KW, Lahad J, Liu J, Lu K, Kuo WL, Smith-McCune K, Fishman D, Gray JW: Amplification of MDS1/EVI1 and EVI1, located in the 3q26.2 amplicon, is associated with favorable patient prognosis in ovarian cancer. Cancer Res. 2007, 67 (7): 3074-3084. 10.1158/0008-5472.CAN-06-2366.CrossRefPubMed
3.
Eder AM, Sui X, Rosen DG, Nolden LK, Cheng KW, Lahad JP, Kango-Singh M, Lu KH, Warneke CL, Atkinson EN: Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc Natl Acad Sci USA. 2005, 102 (35): 12519-12524. 10.1073/pnas.0505641102.PubMedCentralCrossRefPubMed
4.
Nanjundan M, Cheng KW, Zhang F, Lahad J, Kuo WL, Schmandt R, Smith-McCune K, Fishman D, Gray JW, Mills GB: Overexpression of SnoN/SkiL, amplified at the 3q26.2 locus, in ovarian cancers: a role in ovarian pathogenesis. Mol Oncol. 2008, 2 (2): 164-181. 10.1016/j.molonc.2008.05.001.PubMedCentralCrossRefPubMed
5.
Smith DM, Patel S, Raffoul F, Haller E, Mills GB, Nanjundan M: Arsenic trioxide induces a beclin-1-independent autophagic pathway via modulation of SnoN/SkiL expression in ovarian carcinoma cells. Cell Death Differ. 2010, 17 (12): 1867-1881. 10.1038/cdd.2010.53.PubMedCentralCrossRefPubMed
6.
Yatsula B, Lin S, Read AJ, Poholek A, Yates K, Yue D, Hui P, Perkins AS: Identification of Binding Sites of EVI1 in Mammalian Cells. J Biol Chem. 2005, 280 (35): 30712-30722. 10.1074/jbc.M504293200.CrossRefPubMed
7.
Kodigepalli KM, Dutta PS, Bauckman KA, Nanjundan M: SnoN/SkiL expression is modulated via arsenic trioxide-induced activation of the PI3K/AKT pathway in ovarian cancer cells. FEBS Lett. 2013, 587 (1): 5-16. 10.1016/j.febslet.2012.11.003.PubMedCentralCrossRefPubMed
8.
Silverman RH, Halloum A, Zhou A, Dong B, Al-Zoghaibi F, Kushner D, Zhou Q, Zhao J, Wiedmer T, Sims PJ: Suppression of ovarian carcinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1. Cancer Res. 2002, 62 (2): 397-402.PubMed
9.
Bateman A, Finn RD, Sims PJ, Wiedmer T, Biegert A, Soding J: Phospholipid scramblases and Tubby-like proteins belong to a new superfamily of membrane tethered transcription factors. Bioinformatics (Oxford, England). 2009, 25 (2): 159-162. 10.1093/bioinformatics/btn595.CrossRef
10.
Kuo YB, Chan CC, Chang CA, Fan CW, Hung RP, Hung YS, Chen KT, Yu JS, Chang YS, Chan EC: Identification of phospholipid scramblase 1 as a biomarker and determination of its prognostic value for colorectal cancer. Mol Med. 2011, 17 (1–2): 41-47.PubMedCentralPubMed
11.
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E: The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discovery. 2012, 2 (5): 401-404. 10.1158/2159-8290.CD-12-0095.CrossRefPubMed
12.
Wahid F, Shehzad A, Khan T, Kim YY: MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta. 2010, 1803 (11): 1231-1243. 10.1016/j.bbamcr.2010.06.013.CrossRefPubMed
13.
Kortmann J, Sczodrok S, Rinnenthal J, Schwalbe H, Narberhaus F: Translation on demand by a simple RNA-based thermosensor. Nucleic Acids Res. 2011, 39 (7): 2855-2868. 10.1093/nar/gkq1252.PubMedCentralCrossRefPubMed
14.
Wiedmer T, Zhao J, Nanjundan M, Sims PJ: Palmitoylation of phospholipid scramblase 1 controls its distribution between nucleus and plasma membrane. Biochemistry. 2003, 42 (5): 1227-1233. 10.1021/bi026679w.CrossRefPubMed
15.
Der SD, Zhou A, Williams BR, Silverman RH: Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci USA. 1998, 95 (26): 15623-15628. 10.1073/pnas.95.26.15623.PubMedCentralCrossRefPubMed
16.
Dong B, Zhou Q, Zhao J, Zhou A, Harty RN, Bose S, Banerjee A, Slee R, Guenther J, Williams BR: Phospholipid scramblase 1 potentiates the antiviral activity of interferon. J Virol. 2004, 78 (17): 8983-8993. 10.1128/JVI.78.17.8983-8993.2004.PubMedCentralCrossRefPubMed
Metadata
Title
Phospholipid Scramblase 1, an interferon-regulated gene located at 3q23, is regulated by SnoN/SkiL in ovarian cancer cells
Authors
Karthik M. Kodigepalli
Pavana Anur
Paul Spellman
Peter J. Sims
Meera Nanjundan
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2013
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-12-32

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